1. Field of the Invention
This invention relates to sample analysis systems for automated clinical analysis of biological fluid samples and more particularly to an apparatus and method that uses discrete reaction cuvettes and allows simultaneous performance of assays of varied predetermined incubation periods of samples and reagents. Preferably the cuvettes in the clinical analyzer traverse a closed path, such as a circular path of a cuvette ring.
2. Related Prior Art
In one known clinical analyzer, cuvettes for receiving sample and reagent are positioned one behind another in a straight line. The cuvettes are moved along a straight path or track, in a single direction, in movement cycles of fixed time duration. The movement cycles are often referred to as machine cycles or time cycles, (or just cycles, when clearly construed from the context), such as, for example, twenty seconds as used in a known clinical analyzer.
Each cuvette usually contains a discrete assay and each cuvette generally moves a fixed distance during each time cycle to a particular station to undergo a particular function, such as fluid delivery.
Fluid delivery is provided by separate fluid delivery stations that are usually located in a predetermined sequence alongside the straight track. As the cuvettes move progressively along their straight path of travel they pass each of the fluid delivery stations. Each cuvette receives a selected amount of sample, diluent, reagent, etc. from respective fluid delivery stations, depending upon the assay that is associated with each cuvette.
Another known clinical analyzer, as shown in European patent application 014064582, published Jan. 31, 1991, moves cuvettes along a circular path. The disclosed analyzer includes a circular reaction ring or cuvette ring that is rotatable about a central axis such that the cuvettes move along a circular path. Cuvette openings are spaced one next to another at a peripheral portion of the ring, which can accommodate, for example, 100 cuvettes. The cuvette ring rotates at fixed cyclic time intervals of, for example, 30 second duration.
Stations that perform fluid delivery or other functions, are usually provided near the periphery of the cuvette ring.
Whether a clinical analyzer moves cuvettes in a straight line path or along a circular path, or along any other non-linear path, of regular or irregular outline, the fluid delivery stations are usually provided at predetermined sequential locations along the travel path of the cuvette. Fluid delivery stations can also be combined with known robotically movable devices having selected ranges of movement. The collection of the events described in the succeeding paragraphs and the time durations and incubations between them is known as the assay protocol.
Each fluid delivery station may be specialized and set up to perform a specific fluid delivery function such as:                1. dispensation of sample into a cuvette;        2. dispensation of diluent into a cuvette;        3. dispensation of reagent into a cuvette;        4. dispensation of an ancillary material into a cuvette.        
Probes that aspirate and dispense liquids such as reagent can also be washed and re-used before each aspiration/dispensation cycle. Probes that aspirate and dispense sample are sometimes removed and replaced before each aspiration/dispensation cycle.
Cuvettes in a clinical analyzer may also be subjected to the following functions:                1. transfer of a cuvette from its location in a track or cuvette ring to a luminometer;        2. light detection in a luminometer corresponding to a specific assay in a cuvette;        3. installation of a new cuvette in an open cuvette space in a track or cuvette ring if the cuvettes are not re-used;        4. washing of a cuvette after an assay is completed, if the cuvette is to be reused.        
In order for a cuvette in a cuvette ring to receive fluid delivery or other function the cuvette ring rotates a predetermined amount during each time cycle, to move the cuvette step by step in each time cycle to a selected fluid delivery station or location. For example, the cuvette ring can rotate incrementally an amount equivalent to one cuvette space (the cycle distance) during each time cycle of movement.
Generally, the time it takes for a particular cuvette to reach a particular fluid delivery station or location is based on a predetermined incubation period of an earlier fluid delivery to the cuvette. The incubation time between sequential fluid deliveries is a multiple of the cycle duration and the number of time cycles it takes for a cuvette to move from one fluid delivery station to another fluid delivery station. The overall time period for an assay is the number of time cycles it takes for a cuvette to move from a first fluid delivery station to an assay read location where an assay reading can be made by a luminometer, for example.
Known clinical analyzers using a cuvette ring move the cuvettes in a predetermined fixed pattern every cycle, incrementing the ring position by a fixed number of positions every cycle to enable the introduction of a new test. This pattern may have multiple moves and stops to allow cuvettes to be positioned against the fluid delivery stations, wash station or read station, but the pattern repeats exactly every cycle. In one known clinical analyzer, the ring can have three different such patterns but within each such pattern the moves and stops are always the same.
It is well known that the physical layout of known clinical analyzers and the fluid delivery stations including the sequence and spacing of the fluid delivery stations and/or the location of robotically movable fluid delivery devices is generally based on a predetermined incubation period between consecutive fluid dispensations, such as sample dispensation and reagent dispensation.
Thus there is a tie between the incubation periods and the general physical layout of the fluid delivery systems in the known clinical analyzers. This tie severely limits or prevents the clinical analyzer from providing any variation in incubation time for different assays and as a result, the assay protocols are limited to having a few distinct values for the incubation durations.
I have found that I can break the tie between the physical layout of the fluid delivery system and assay timing by providing variable cuvette carrier motions in a fixed time cycle rather than be limited by non-variable movement of cuvettes along a circular path. Insofar as I am aware non-variable movement of cuvettes for a particular time cycle is prevalent in all known clinical analyzers that use a cuvette carrier.
I have discovered that by moving a cuvette in a cuvette ring from an initial selected reference location variable distances in selected directions to other selected locations for fluid delivery without waiting for fixed incremental ring movements in one direction, I can provide different incubation times between assay events that vary continuously, in multiples of the time cycle, within a wide range. This, in turn, provides the assay developers with much greater latitude in choosing the optimal incubation periods for each assay. Once the optimal incubation time periods are determined, the scheduling algorithms described in succeeding paragraphs will allow multiple assays of varying assay protocols to run in random-access.
By implementing variable movement of cuvettes in selected directions in a given time cycle I can also reduce the number of normally required fluid delivery stations from, for example, five to two. I can obtain this reduction in fluid delivery stations by moving different cuvettes, different distances at different incubation time intervals to two different fluid delivery stations (variable movement) for example, rather than have all cuvettes move at the same incubation time intervals in the same direction to each of five selected consecutive fluid delivery stations, for example.
In addition, I have found that with variable movement of cuvettes along a circular path in selected directions I can use priorities other than sequentially located fluid delivery stations to determine the physical layout of a clinical analyzer. For example I can conveniently locate fluid delivery stations based on conveniently available space and based on the ease of permitting access to the various fluid delivery and function stations in the clinical analyzer. In addition I can provide versatility in a fluid delivery station by enabling the same fluid delivery station to deliver one or more reagents and ancillary materials to a cuvette.
Corresponding reference characters indicate corresponding parts throughout the several views of the drawings.